Lyme neuroborreliosis (LNB) is an increasingly prevalent cause of neurological disease in the world. The infection results in chronic meningitis, cranial nerve lesions, chronic disorders of memory and cognitive functioning, and peripheral nerve damage. Very little is known about pathogenesis of the infection in the central nervous system (CNS). This ignorance about the pathogenesis of LNB has prompted laborious and excessively expensive diagnostic procedures, as well as bizarre and frequently toxic treatments: For instance, we do not know: how frequently the spirochete invades the CNS after intradermal injection how long the infection persists in the CNS the CNS cell type and location infected whether the immune system plays a significant role in the CNS infection whether spirochetes invade peripheral nerves This project will address these areas of ignorance, using a model of LNB in Rhesus macaques recently developed in our laboratory. The information gained will lead to an understanding of pathogenesis as well as the development of rationale diagnostic strategies and safe, effective therapy. It will also lead to a greater understanding of chronic infections of the CNS.